Crystal engineering of some bioflavonoids design Synthesis and evaluation

Abstract

Crystal engineering technique provides manifold opportunities to selectively ameliorate the physicochemical properties of a crystalline material on account of the knowledge on crystallization procedures and the molecular properties of an active component. The work in this thesis illustrates the implementation of crystal engineering approach for the improvement of the biopharmaceutical parameters of daidzein, genistein, fisetin and chrysin by applying cocrystallization approach. To overcome this issue, cocrystallization was applied since this approach has not been explored much for the polyphenolic molecules. These molecules have various competitive sites for hydrogen bonding (hydroxyls and carbonyl), in its molecular skeleton, offering the possibility of cocrystal formation. The systematic experimental procedure had lead to the formation of cocrystals of bioflavonoidal molecules with the coformers of GRAS (Generally Recognized as Safe) status. Mechanochemical grinding has been utilized to prepare the cocrystals and prepared cocrystals were characterized via, DSC, FT-IR, PXRD and SSNMR. The crystal structure determined was further manifested by the distinct changes in chemical shifts revealed by ssNMR. The solubility studies in physiologically similar aqueous medium showed improvement in the dissolution profile with a 2-3 manifold increase in the peak concentration of the selected flavonoids reached by the cocrystals. The evaluation of the pharmacokinetic parameter showed an improvement when compared to the parent constituents.The DDPH assay for antioxidant effect and antihemolytic effect in rat RBC s followed by carragenan induced paw edema model for determining the anti-inflammation activity of the cocrystals showed improved activities when comparison to respective flavonoidal molecules. Hence from the present work, it can be concluded that cocrystallization is a viable approach to resolve the solubility and bioavailability issues that circumvent the use of potential bioflavonoidal molecules.